Semaglutide administered weekly at 2.4 mg significantly reduces major adverse cardiovascular events (MACE) by 20% in adults with pre-existing cardiovascular disease and obesity without diabetes.
Mediation analysis of the SELECT trial investigated changes in traditional cardiovascular risk factors including body weight, waist circumference, inflammatory markers (hsCRP), glycemia (HbA1c), lipids, blood pressure, and renal markers as contributors to cardiovascular benefit.
While semaglutide improved all measured mediators, individually none fully explained the cardiovascular risk reduction with wide confidence intervals and unreliable estimates especially for weight-related parameters.
Combined analysis suggests known risk factors mediate approximately one-third to nearly half of the cardiovascular benefit; the remainder likely involves other unexplored pathways.
